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Lasso-inspired peptides with distinct antibacterial mechanisms

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Abstract

Microcin J25 (MccJ25) is an antibacterial peptide with a peculiar molecular structure consisting of 21 amino acids and a unique lasso topology that makes it highly stable. We synthesized various MccJ25-derived peptides that retained some of the inhibitory activity of the native molecule against Salmonella enterica and Escherichia coli. Of the tested peptides, C1, 7-21C and WK_7-21 were the most inhibitory peptides (MIC = 1–250 µM), but all three were less potent than MccJ25. While MccJ25 was not active against Gram-positive bacteria, the three derived peptides were slightly inhibitory to Gram-positive bacteria (MIC ≥ 250 µM). At 5 µM, C1, 7-21C and WK_7-21 reduced E. coli RNA polymerase activity by respectively, 23.4, 37.4 and 65.0 %. The MccJ25 and its derived peptides all appeared to affect the respiratory apparatus of S. enterica. Based on circular dichroism and FTIR spectroscopy, the peptides also interact with bacterial membrane phospholipids. These results suggest the possibility of producing potent MccJ25-derived peptides lacking the lasso structure.

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Acknowledgments

The authors express their gratefulness to Sophie Sablé for providing the E. coli strain harboring the plasmid pTUC202. François Bédard thanks the National Sciences and Engineering Research Council of Canada (NSERC) and the Fonds d’enseignement et de recherche de la Faculté de pharmacie de l’Université Laval for scholarships. The financial support of the Fonds de recherche du Québec-Nature et technologies (FQRNT) is gratefully acknowledged.

Conflict of interest

The authors declare that no personal relationship or interest had any influence on the design, execution, analysis or interpretation of the experiments reported herein.

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  1. Ahmed Gomaa

    Present address: Food Technology and Nutrition Research Division, Food Science and Nutrition Department, National Research Center, Cairo, Egypt

Authors and Affiliations

  1. STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, Québec, QC, G1V 0A6, Canada

    Riadh Hammami, Ahmed Gomaa, Muriel Subirade & Ismail Fliss

  2. Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, CHU de Québec Research Centre, Québec, QC, G1V 4G2, Canada

    François Bédard & Eric Biron

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  1. Riadh Hammami
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Hammami, R., Bédard, F., Gomaa, A. et al. Lasso-inspired peptides with distinct antibacterial mechanisms. Amino Acids 47, 417–428 (2015). https://doi.org/10.1007/s00726-014-1877-x

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